EXSS is Exercising Science Solutions for Public Impact

Impact of Physical Activity on Biomarker of Aging and Body Composition among Breast Cancer Survivors Age 65 and Older

This week’s EXSS Impact post highlights new interdisciplinary research being conducted by Dr. Claudio Battaglini and his collaborators Drs. Hyman Muss, Ned Sharpless, and Kristen Nyrop. This collaborative effort can provide important findings on ways to combat the ramifications of breast cancer treatments. Many thanks to Claudio and his collaborators for providing this week’s EXSS Impact story.

What was the purpose of doing this study?

Breast cancer is the most common cancer among women in general and among older women in particular. Adjuvant chemotherapy has played a major role in improving survival in both younger and older patients, but in older women, especially, its associated toxicities can lead to declines in function, quality of life, and even survival. For clinicians treating older women with a breast cancer diagnosis, how their patients survive and thrive during and after adjuvant chemotherapy is as important as preventing cancer recurrence and prolonging life. Toxicities that result in decreased physical activity and increased fatigue can lead to chronic detrimental changes in body composition, including loss of lean body mass, loss of muscle mass, and an increase in adipose tissue. Interventions to decrease these risks are needed. The overall goal of this research is to identify whether a home-based physical activity program initiated during adjuvant chemotherapy can attenuate the molecular and clinical ramifications of adjuvant chemotherapy on the aging process in a sample of breast cancer patients age 65 or older. Specifically, this study will investigate the impact of the exercise program on changes pre- and post-chemotherapy: (1) in a gene that is a biomarker of aging (p16INK4a) and (2) lean body mass, physical function, fatigue, and quality of life. The study will also evaluate how data from a wireless activity tracker correlates with measures of function and quality of life during chemotherapy. If it is shown that this easy-to-implement physical activity intervention can maintain function and lessen toxicity among older breast cancer patients receiving chemotherapy, it would be ideal for incorporation into adjuvant treatment in both academic and community-based cancer care settings.

What are we currently doing and what we expect to find in this study?

The overall goal of this research is to identify whether a home-based exercise program initiated during adjuvant chemotherapy for breast cancer can attenuate the molecular and clinical ramifications of chemotherapy on the aging process. Specifically, we hypothesize that exercise will lessen fatigue, maintain or improve lean body mass during chemotherapy, and also attenuate the dramatic and sustained increase in p16INK4a expression that is associated with both chemotherapy administration and advancing age. If it is shown that this simple home-based walking intervention can maintain function and lessen toxicity, it would be ideal for implementation into adjuvant treatment in both academic and community settings.

The intervention is self-directed, home-based walking with the goal of achieving the ACS guideline recommended level of 150 minutes per week. Study participants receive a FitBit and are asked to maintain a daily exercise diary. FitBit data are downloaded during every chemotherapy visit. We have tested this intervention is a pilot study (LCCC1226) of women 65 or older receiving chemotherapy for breast cancer and have found the program feasible, safe and promising.

Measures of engagement in physical activity: Questionnaires including items that inquire about the number of minutes per day and the number of days per week that participants engage in walking for pleasure or exercise.

Our target recruitment over a 4 year period is 100. Recruitment has been underway for a couple of months and 8 women have been consented into the study. All participants will do the walking intervention; the control group is a random sample of 100 participants in an on-going study collecting similar measures but there is no physical activity intervention.

How do these findings impact the public?

The recent and timely Institute of Medicine (IOM) report Delivering high-quality cancer care: Charting a new course for a system in crisis” clearly states that “responses to cancer diagnoses and treatments are certainly influenced by the aging process and that in order to provide quality cancer care for older adults, we need to bolster our research evidence within this population” and that “addressing the unique needs of an aging population is central to improving the quality of cancer care.” Breast cancer is the most commonly diagnosed cancer in American women and the second leading cause of cancer deaths. The greatest risk factor for breast cancer is age and, as the population ages, there will be a dramatic increase in the burden of breast cancer among older women. Adjuvant chemotherapy decreases the risks of relapse and mortality from breast cancer; however, older patients are at increased risk for chemotherapy toxicity, including an increased risk of treatment-related mortality and loss of function. A feared toxicity of chemotherapy is loss of function. Exercise has been shown to maintain function and improve quality of life in numerous cancer settings. Maintaining physical activity during chemotherapy is challenging for all patients, especially those who are older. This study is innovative in using a proven and scalable walking intervention to attenuate the rise of a novel biomarker of cellular senescence and aging, p16INK4a, that dramatically and irreversibly increases with chemotherapy. If it is shown that this simple intervention can maintain function and lessen toxicity it would be ideal for implementation into adjuvant treatment in both academic setting as well as community settings.

Name of all the sites involved in the study: UNC Health Care (Chapel Hill), Rex UNC Health Care (Raleigh). Negotiations are underway with MD Anderson (Houston), Ohio State University, and University of Louisville.

Name of the funding source and amount given to research team to conduct the study: Kay Yow Jimmy V Foundation (Raleigh NC) – $1 million